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Biomedical subjects

E Yu

Publications and source records attributed to E Yu.

At least 37 records · Page 2Linked to original sources

Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta.

A cDNA encoding a novel multispecific organic anion transporter, OAT4, was isolated from a human kidney cDNA library. The OAT4 cDNA consisted of 2210 base pairs that encoded a 550-amino acid residue protein with 12 putative membrane-spanning domains. The amino acid sequence of OAT4 showed 38 to 44% identity to those of other members of the OAT family. Northern blot analysis revealed that OAT4 mRNA is abundantly expressed in the placenta as well as in the kidney. When expressed in Xenopus oocytes, OAT4 mediated the high affinity transport of estrone sulfate (K(m) = 1.01 microM) and dehydroepiandrosterone sulfate (K(m) = 0.63 microM) in a sodium-independent manner. OAT4 also mediated the transport of ochratoxin A. OAT4-mediated transport of estrone sulfate was inhibited by several sulfate conjugates, such as p-nitrophenyl sulfate, alpha-naphthyl sulfate, beta-estradiol sulfate, and 4-methylumbelliferyl sulfate. By contrast, glucuronide conjugates showed little or no inhibitory effect on the OAT4-mediated transport of estrone sulfate. OAT4 interacted with chemically heterogeneous anionic compounds, such as nonsteroidal anti-inflammatory drugs, diuretics, sulfobromophthalein, penicillin G, and bile salts, whereas tetraethylammonium, an organic cation, did not. OAT4 is the first member of the multispecific organic anion transporter family, which is expressed abundantly in the placenta. OAT4 might be responsible for the elimination and detoxification of harmful anionic substances from the fetus.

Amino Acid Sequence↗

ROG, repressor of GATA, regulates the expression of cytokine genes.

GATA-3 is a T cell-specific transcription factor and is essential for the development of the T cell lineage. Recently, it was shown that the expression of GATA-3 is further induced in CD4+ helper T cells upon differentiation into type 2 but not type 1 effector cells. Here, we report the molecular cloning of a GATA-3 interacting protein, repressor of GATA (ROG). ROG is a lymphoid-specific gene and is rapidly induced in Th cells upon stimulation with anti-CD3. In in vitro assays, ROG represses the GATA-3-induced transactivation. Furthermore, overexpression of ROG in Th clones inhibits the production of Th cytokines. Taken together, our results suggest that ROG might play a critical role in regulating the differentiation and activation of Th cells.

Amino Acid Sequence↗

Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: histopathologic findings of renal allografts with proteinuria.

The proteinuria in renal allograft recipients has been regarded as a sign of poor prognosis. The causes of post-transplant proteinuria include chronic rejection, chronic transplant glomerulopathy, glomerulonephritis (GN), acute rejection, and cyclosporine nephrotoxicity. Among them, chronic rejection is known to be most frequent. We analyzed the histopathologic findings of renal allograft biopsies in 197 Korean recipients with proteinuria. Among them, 26 patients developed proteinuria over 500 mg/d. All patients received baseline immunosuppression with cyclosporine. From 26 patients with post-transplant proteinuria, 29 biopsies were performed and their histologic diagnoses were immunoglobulin A nephropathy (IgAN) in 17, IgAN combined with chronic allograft nephropathy in 1, focal segmental glomerulosclerosis in 2, crescentic GN in 1, membranous GN in 1, diabetic nephropathy in 1, acute tubulointerstitial nephritis in 1, and chronic rejection in 3 biopsies. The remaining two biopsies showed nonspecific findings. The most common cause of post-transplant proteinuria was IgAN (62% of biopsies). The incidence of chronic rejection was relatively low and predominant cyclosporine-associated changes were not observed. In conclusion, our data suggest that the main causes of post-transplant proteinuria in Korea are primary glomerulonephritides rather than chronic rejection or cyclosporine nephrotoxicity, and the kidney allograft biopsies from patients with proteinuria should be handled as native kidney.

Adult↗

Expression of promyelocytic leukaemia protein in thyroid neoplasms.

AIMS: Promyelocytic leukaemia protein (PML) is an oncoprotein involved in the pathogenesis of acute promyelocytic leukaemia and is localized in distinct PML nuclear bodies. Our previous observation of overexpression of the PML in hormone-sensitive normal tissues and malignant solid tumours, including the thyroid, led to this analysis of the PML expression in various thyroid neoplasms to characterize the importance of the PML in thyroid carcinogenesis. METHODS AND RESULTS: Immunohistochemistry was performed on paraffin-embedded tissue samples from 106 thyroid neoplasms after antigen retrieval by microwave. Immunoblotting was done with fresh frozen tissues in a few tumours. The PML was strongly expressed in all papillary carcinomas in diffuse or ball-shaped patterns. In the follicular neoplasms, the PML expression was variable, but there was no significant difference between adenomas and carcinomas. In the medullary carcinomas, the PML expression was either not detectable or was lower than in non-neoplastic thyroids. Quantitatively different expression of the PML in various thyroid neoplasms was confirmed by immunoblotting. CONCLUSION: A significant difference of the PML expression according to the type of thyroid neoplasms suggests that the PML is important in papillary thyroid carcinomas, and furthermore, that PML expression may be used in differential diagnosis of thyroid neoplasms.

Adenocarcinoma↗

Merkel cell carcinoma of the skin.

BACKGROUND: Neuroendocrine/Merkel cell carcinoma (MCC) of the skin is an uncommon tumour. Currently, there are only limited data available on the natural history, prognostic factors, and patient management of MCC. OBJECTIVES: To review our experience and build the largest database from the literature. METHODS: Twenty-eight cases from the London Regional Cancer Center were combined with 633 cases obtained from the literature searched in English, French, German, and Chinese for the years 1966 to 1998. The database included age, sex, initial disease status at presentation to the clinic, site of primary, any coexisting disease, any previous irradiation, sizes of primary/nodal/distant metastases, management details, and final disease status. A new modified staging system was used: stage Ia (primary disease only, size > 2 cm), stage Ib (primary disease only, size > 2 cm); stage II (regional nodal disease), and stage III (beyond regional nodes and/or distant disease). RESULTS: Age > 65 years, male sex, size of primary > 2 cm, truncal site, nodal/distant disease at presentation, and duration of disease before presentation (< or =3 months) were poor prognostic factors. Surgery was the initial treatment of choice and it significantly improved overall survival (p =.004). CONCLUSIONS: We identified poor prognostic factors that may necessitate more aggressive treatment. The suggested staging system, incorporating primary tumour size, accurately predicted outcomes.

Aged↗

Chemotherapy in neuroendocrine/Merkel cell carcinoma of the skin: case series and review of 204 cases.

PURPOSE: To study the use of chemotherapy for Merkel cell carcinoma (MCC) of the skin. PATIENTS AND METHODS: Twenty-five cases of MCC were treated at the London Regional Cancer Center between 1987 and 1997. Thirteen cases treated with chemotherapy were reviewed with 191 cases from the literature. RESULTS: At presentation, 24 patients had localized skin lesions (stage I) and one had locoregional involvement (stage II). Among the nine cases with recurrent nodal disease, six had chemotherapy as a component of salvage treatment. They were all free of disease at a median of 19 months (range, 12 to 37 months). In contrast, two patients who had salvage radiotherapy alone died of disease. Overall survival (OS) and disease-free survival (DFS) were 59% and 43%, respectively, at two years. Median OS and DFS were 29 months (range, 1 to 133 months) and 9 months (range, 1 to 133 months), respectively. Nodal disease developed in 12 (50%) of 24 patients with stage I disease, and distant metastases developed in six (25%) of 24. Including those from the literature, there were 204 cases treated with chemotherapy. Cyclophosphamide/doxorubicin (or epirubicin)/vincristine combination +/- prednisone was the most commonly used chemotherapy regimen (47 cases), with an overall response rate of 75.7% (35.1% complete, 35. 1% partial, and 5.4% minor responses). Etoposide/cisplatin (or carboplatin) was the next most commonly used regimen (27 cases), with an overall response rate of 60% (36% complete and 24% partial responses). The difference in response rate was not statistically significant (P =.19). Among the 204 cases, there were seven (3.4%) toxic deaths. CONCLUSION: Chemoradiation for locally recurrent or advanced disease may be an option for patients with a good performance status.

Aged↗

CT features of metastatic linitis plastica to the rectum in patients with peritoneal carcinomatosis.

OBJECTIVE: We examined the CT features of 22 patients with metastatic linitis plastica to the rectum. CONCLUSION: Metastatic linitis plastica to the rectum should be considered when CT shows a long segment of circumferential rectal wall thickening, especially in patients with peritoneal carcinomatosis from gastric cancer. In such patients, CT helps avoid unnecessary extensive surgery.

Adult↗

Three cases of pancreas allograft dysfunction.

We present dincopathologic features of three cases of biopsy-proven pancreas allograft dysfunction in Korea. All patients had advanced insulin-dependent diabetes mellitus (IDDM). Case 1 was a 30-year-old woman who underwent a simultaneous pancreas-kidney transplantation. Urinary infection developed 6 days after the operation, which remitted and reappeared, when urine amylase level was normal. Since the 55th day after the operation, intermittent hematuria has persisted. Cytomegalovirus inclusions were detected on the urinary bladder and grafted duodenal mucosa. The graft was removed due to perforation of the grafted duodenum and panperitonitis. Case 2 was a 27-year-old man undergoing pancreas transplantation alone (PTA). Ten days after the transplatation, the level of 24 urine amylase decreased and the graft was not delineated by 99mTc DTPA scintigraphy. Allograft needle biopsy revealed multiple acinar cell necrosis and mild lymphocytic infiltration which were compatible with mild acute rejection. Case 3 was a 25-year-old man undergoing cadevaric PTA. Three months after the transplantation, graft was removed due to gastric perforation associated with cytomegalovirus and angiodestructive fungal infection. Various causes of pancreas allograft dysfunction can be diagnosed by needle biopsy, thus appropriate biopsy specimen should be taken using improved biopsy technique.

Adult↗

Fibrosing cholestatic hepatitis: a report of three cases.

Fibrosing cholestatic hepatitis is an aggressive and usually fatal form of viral hepatitis in immunosuppressed patients. We report three cases of fibrosing cholestatic hepatitis in various clinical situations. Case 1 was a 50-year-old man who underwent a liver transplant for hepatitis B virus (HBV)-associated liver cirrhosis. Two and a half years after the transplant, he complained of fever and jaundice, and liver enzymes were slightly elevated. Serum HBsAg was positive. Case 2 was a 30-year-old man in an immunosuppressed state after chemotherapy for acute lymphoblastic leukemia. He was a HBV carrier. Liver enzymes and total bilirubin were markedly elevated. Case 3 was a 50-year-old man who underwent renal transplantation as a known HBV carrier. One year after the transplant, jaundice developed abruptly, but liver enzymes were not significantly elevated. Microscopically lobules were markedly disarrayed, showing ballooning degeneration of hepatocytes, prominent pericellular fibrosis, and marked canalicular or intracytoplasmic cholestasis. Portal inflammation was mild, but interphase activity was definite and cholangiolar proliferation was prominent. Hepatocytes were diffusely positive for HBsAg and HBcAg in various patterns. Patients died of liver failure within 1 to 3 months after liver biopsy in spite of anti-viral treatment.

Adult↗

Intracardiac extension of intravenous leiomyomatosis in a pregnant woman: A case report and review of the literature.

Intravenous leiomyomatosis is an uncommon clinical entity characterized by the growth of a benign, smooth muscle tumour within the venous system. Intracardiac extension of this tumour is rare, and approximately 35 cases have been reported in the literature. The second case of massive intracardiac extension of intravenous leiomyomatosis is reported in a pregnant patient diagnosed after the unusual presentation of seizure activity. Tumours were successfully removed from the right internal iliac vein, inferior vena cava, and right atrium and ventricle in a single-stage operation using cardiopulmonary bypass and circulatory arrest. Concomitant total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Nine months after diagnosis, the patient was evaluated for recurrent disease. A review of the literature from 1994 to 1998 is presented.

Adult↗

The assessment of technical skills in a cardiology training program: is the ITER sufficient?

Diagnostic coronary angiography is an important tool in the assessment of heart disease. No objective data are available regarding the best method of training or testing a cardiology trainee's skill in the performance of this procedure. Training guidelines are based on the consensus opinions of experts in the field, and the assessment of proficiency is relegated to a generalized in-training evaluation report (ITER). However, is an ITER sufficient? The current modes of assessment are examined, with the question of whether a more comprehensive and valid assessment process is needed.

Cardiac Catheterization↗

Mitogenic signaling by ATP/P2Y purinergic receptors in astrocytes: involvement of a calcium-independent protein kinase C, extracellular signal-regulated protein kinase pathway distinct from the phosphatidylinositol-specific phospholipase C/calcium pathway.

Activation of ATP/P2Y purinergic receptors stimulates proliferation of astrocytes, but the mitogenic signaling pathway linked to these G-protein-coupled receptors is unknown. We have investigated the role of extracellular signal-regulated protein kinase (ERK) in P2Y receptor-stimulated mitogenic signaling as well as the pathway that couples P2Y receptors to ERK. Downregulation of protein kinase C (PKC) in primary cultures of rat cerebral cortical astrocytes greatly reduced the ability of extracellular ATP to stimulate ERK. Because occupancy of P2Y receptors also leads to inositol phosphate formation, calcium mobilization, and PKC activation, we explored the possibility that signaling from P2Y receptors to ERK is mediated by a phosphatidylinositol-specific phospholipase C (PI-PLC)/calcium pathway. However, neither inhibition of PI-PLC nor chelation of calcium significantly reduced ATP-stimulated ERK activity. Moreover, a preferential inhibitor of calcium-dependent PKC isoforms, Gö 6976, was significantly less effective in blocking ATP-stimulated ERK activity than GF102903X, an inhibitor of both calcium-dependent and -independent PKC isoforms. Furthermore, ATP stimulated a rapid translocation of PKCdelta, a calcium-independent PKC isoform, but not PKCgamma, a calcium-dependent PKC isoform. ATP also stimulated a rapid increase in choline, and inhibition of phosphatidylcholine hydrolysis blocked ATP-evoked ERK activation. These results indicate that P2Y receptors in astrocytes are coupled independently to PI-PLC/calcium and ERK pathways and suggest that signaling from P2Y receptors to ERK involves a calcium-independent PKC isoform and hydrolysis of phosphatidylcholine by phospholipase D. In addition, we found that inhibition of ERK activation blocked extracellular ATP-stimulated DNA synthesis, thereby indicating that the ERK pathway mediates mitogenic signaling by P2Y receptors.

Animals↗

Progressive changes of the nuclear matrix protein composition in diethylnitrosamine-induced rat hepatocarcinogenesis.

The nuclear matrix proteins (NMPs) consist of common and tissue-specific nuclear proteins, which can be altered by extracellular environments such as radiation, chemicals and virus infection. Thus, NMP profiles were analyzed in diethylnitrosamine (DEN)-treated rat liver. Male F344 rats (6 weeks old) were treated continuously with DEN (40 ppm) in drinking water. All animals were sacrificed at 10, 20 or 30 weeks during the experiment. The profiles of NMPs and cytoskeletal proteins (CSPs) progressively changed in their number and amount in DEN-treated rats. Four peptides increased in their relative amounts, while three decreased in the 10- and 20-week groups. Many NMPs were detected in DEN-induced hepatocellular carcinomas. These results suggest that the alteration of the NMPs may be involved in DEN-induced hepatocarcinogenesis.

Animals↗

Acute inflammation of the proliferative zone of gastric mucosa in Helicobacter pylori gastritis.

The neutrophilic infiltration has been regarded to represent the activity of Helicobacter pylori gastritis. It may involve the epithelium and/or lamina propria. The incidence and degree of the two types of infiltration do not correlate with each other frequently. We correlated the two types of neutrophilic infiltration with H. pylori infection and other pathologic parameters respectively in 300 randomly selected gastric biopsies as well as serial biopsies from a separate group of 95 patients who were treated for H. pylori infection. The "random biopsies" had chronic gastritis of various degrees, and the organisms were identified in 239 cases (79.7%); in the "treated group," the organisms disappeared completely in 62 cases (65.3%). Characteristically, the intraepithelial neutrophilic infiltration was predominantly localized to the proliferative zone of the gastric mucosa (zone 2) where the density of H. pylori was considerably lower than the surface epithelium. In the "random biopsies," both acute epithelial and interstitial neutrophilic infiltration correlated significantly (p < 0.01) with the H. pylori infection. In the "treated group," however, only acute epithelial inflammation correlated significantly (p < 0.01) with the eradication of infection while acute interstitial inflammation did not. Acute epithelial inflammation was no less frequently present in advanced chronic gastritis than in early chronic gastritis. Acute epithelial inflammation of the proliferative zone is a characteristic pathologic finding of H. pylori gastritis, and appears to be directly associated with the pathogenesis of H. pylori gastritis and its progression.

Biopsy↗